BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway.

BACKGROUND: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms. METHODS: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism. RESULTS: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway. CONCLUSION: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis.

Protective effect of Nrf2 in periodontitis - A preclinical systematic review and meta-analysis.

OBJECTIVE: Periodontitis is an inflammatory disease, while Nuclear factor erythroid-2 related factor 2 (Nrf2) acts a significant part in antioxidant, anti-inflammatory and immune response. However, the evidence in preclinical studies to certify Nrf2 can slow down the progression of periodontitis or facilitate its recovery is not enough. The present report aims to investigate the functional implications of Nrf2 in animal periodontitis models by evaluating the changes of Nrf2 levels and analyzing the clinical benefits of Nrf2 activation in the same models. DESIGN: We searched PubMed, Web of Science, EBSCO, CNKI, VIP, Wan Fang databases. The random-effects model was used to evaluate the mean differences (MD) and 95 % confidence intervals (95%CI) when the units of measurements of outcome indicators were the same, in contrast, the standardized mean differences (SMD) and 95%CI were evaluated while the units were different. RESULTS: 8 studies were included for quantitative synthesis. Compared with healthy groups, the expression of Nrf2 was markedly lower in periodontitis groups (SMD: -3.69; 95%CI: -6.25, -1.12). After administration of kinds of Nrf2-activators, a significant increase in Nrf2 levels (SMD: 2.01; 95%CI: 1.27, 2.76) was accompanied by a decrease in distance between cementoenamel junction and alveolar bone crest (CEJ-ABC) (SMD: -2.14; 95%CI: -3.29, -0.99) and an improvement of bone volume/tissue volume (BV/TV) (SMD:17.51; 95%CI: 16.24, 18.77) was evaluated compared with periodontitis groups. CONCLUSIONS: Nrf2 has a certain protective effect on periodontitis, however, the specific role Nrf2 plays in the development and severity of periodontitis remains to be demonstrated. PROSPERO registration number: CRD42022328008.

Effect of 45S5 bioactive glass on the microshear bond strength of dental fluorosis.

The aim of this in vitro study was to estimate the effect of the species concentration of 45S5 bioactive glass (BAG) used as pretreatment on the microshear bond strength (MSBS) of dental fluorosis (DF). Based on the Thylstrup and Fejerskov index, 80 teeth were randomly divided equally into four groups: TFI 0, sound dentin; TFI 1-3, mild fluorosis; TFI 4-5, moderate fluorosis; and TFI 6-9, severe fluorosis. Each group was randomized into five subgroups. After preparing the dentin hypersensitivity model of DF, the dentin was pretreated as follows, Subgroup 1: deionized water (Control group); Subgroup 2: 1% BAG; Subgroup 3: 5% BAG; Subgroup 4: 10% BAG, and Subgroup 5: 20% BAG. Stochastically one specimen was selected from each subgroup for scanning electron microscope and energy dispersive spectrometer analysis. After being made of resin-tooth bonding samples, the remains were in water bath at 37 °C for 24 hr. Subsequently, samples from each subgroup were randomly selected to test MSBS without aging, or after a thermocycle of 5,000 and 10,000 times, respectively. The fracture modes were analyzed. Compared with the group of 1% BAG and Control, the exposure area of tubules in 5%, 10%, and 20% BAG group had significant difference (p < .05). MSBS results indicated that there were significant differences between 10% BAG with other groups. The 20% BAG group showed the lowest MSBS among all groups. Pretreatment of 10% BAG solution may be conductive to enhance the bond strength of DF, while 20% BAG solution adversely.